ArticleACS chemical biology2007
Mechanisms of resistance to an amino acid antibiotic that targets translation.
Article in ACS chemical biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- Riboswitch-targeted improvement of lysine production in Bacillus and Priestia species.NPJ science of food · 2026Article
- Structural basis of specific lysine transport by Pseudomonas aeruginosa permease LysP.Nature communications · 2025Article
- Plant amino acid analogues as antimicrobial agents.Amino acids · 2025Review
- The current riboswitch landscape inMicrobiology (Reading, England) · 2024Review
- RNA cis-regulators are important for Streptococcus pneumoniae in vivo success.PLoS genetics · 2024Article
- Creating Single-Cell Protein-ProducingScientifica · 2024Article
- Characterization of the glmS Ribozymes from Listeria Monocytogenes and Clostridium Difficile.Chemistry (Weinheim an der Bergstrasse, Germany) · 2023Article
- A Riboswitch-Driven Era of New Antibacterials.Antibiotics (Basel, Switzerland) · 2022Review
- Brief considerations on targeting RNA with small molecules.Faculty reviews · 2022Review
- A New Promising Anti-Infective Agent Inhibits Biofilm Growth by Targeting Simultaneously a Conserved RNA Function That Controls Multiple Genes.Antibiotics (Basel, Switzerland) · 2021Article
- Small-Molecule Antibiotics Inhibiting tRNA-Regulated Gene Expression Is a Viable Strategy for Targeting Gram-Positive Bacteria.Antimicrobial agents and chemotherapy · 2020Article
- Parallel Discovery Strategies Provide a Basis for Riboswitch Ligand Design.Cell chemical biology · 2020Article
- SPRINT: a Cas13a-based platform for detection of small molecules.Nucleic acids research · 2020Article
- Deep scanning lysine metabolism inMolecular systems biology · 2018Article
- Structure-Activity Relationship of Flavin Analogues That Target the Flavin Mononucleotide Riboswitch.ACS chemical biology · 2018Article
- Emerging applications of riboswitches - from antibacterial targets to molecular tools.Journal of applied genetics · 2016Review
- De Novo Guanine Biosynthesis but Not the Riboswitch-Regulated Purine Salvage Pathway Is Required for Staphylococcus aureus Infection In Vivo.Journal of bacteriology · 2016Article
- Two ATP-binding cassette transporters involved in (S)-2-aminoethyl-cysteine uptake in thermus thermophilus.Journal of bacteriology · 2013Article
- Structure and mechanism of purine-binding riboswitches.Quarterly reviews of biophysics · 2012Review
- Riboswitches: discovery of drugs that target bacterial gene-regulatory RNAs.Accounts of chemical research · 2011Review
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Structural and functional diversity among the aminoacyl-tRNA synthetases prevent infiltration of the genetic code by noncognate amino acids. To explore whether these same features distinguish the synthetases as potential sources of resistance against antibiotic amino acid analogues, we investigated bacterial growth inhibition by S-(2-aminoethyl)-L-cysteine (AEC). Wild-type lysyl-tRNA synthetase (LysRS) and a series of active site variants were screened for their ability to restore growth of an Escherichia coli LysRS null strain at increasing concentrations of AEC. While wild-type E. coli growth is completely inhibited at 5 microM AEC, two LysRS variants, Y280F and F426W, provided substantial resistance and allowed E. coli to grow in the presence of up to 1 mM AEC. Elevated resistance did not reflect changes in the kinetics of amino acid activation or tRNA (Lys) aminoacylation, which showed at best 4-6-fold improvements, but instead correlated with the binding affinity for AEC, which was decreased approximately 50-fold in the LysRS variants. In addition to changes in LysRS, AEC resistance has also been attributed to mutations in the L box riboswitch, which regulates expression of the lysC gene, encoding aspartokinase. The Y280F and F426W LysRS mutants contained wild-type L box riboswitches that responded normally to AEC in vitro, indicating that LysRS is the primary cellular target of this antibiotic. These findings suggest that the AEC resistance conferred by L box mutations is an indirect effect resulting from derepression of lysC expression and increased cellular pools of lysine, which results in more effective competition with AEC for binding to LysRS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.